Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Recurrence

Lymphoma

Hodgkin Disease

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Hodgkin Lymphoma

Rigid Spine Syndrome

All Drugs and Chemicals

Anti-Infective Agents

Antirheumatic Agents

Dermatologic Agents

Anti-Arrhythmia Agents

Channel Blockers

Vasodilator Agents

Antineoplastic Agents

Bone Density Conservation Agents

Antibodies

Antibodies, Monoclonal

Cyclosporine

Cyclosporins

Immunoglobulins

Verapamil

Brentuximab Vedotin

Antineoplastic Agents, Immunological

Immunoglobulins, Intravenous

Immunoconjugates

Immunologic Factors

Enzyme Inhibitors

Immunosuppressive Agents

Clotrimazole

Miconazole

Antifungal Agents

Calcineurin Inhibitors

Immunotoxins

Calcium

Calcium Channel Blockers

Calcium, Dietary

Hormones

Patients receive cyclosporine PO BID on days 1-5, verapamil hydrochloride PO QID on days 1-5, and brentuximab vedotin IV over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Pharmacokinetic Study

Verapamil Hydrochloride

Alex F Herrera

This phase I trial studies the side effects and best dose of brentuximab vedotin and cyclosporine when given together with verapamil hydrochloride in treating patients with Hodgkin lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30 positive cancer cells in a targeted way and delivers vedotin to kill them. Immunosuppressive therapies, such as cyclosporine, may improve bone marrow function and increase blood cell counts. Verapamil hydrochloride may increase the effectiveness of brentuximab vedotin by overcoming drug resistance of the cancer cells. Giving brentuximab vedotin, cyclosporine, and verapamil hydrochloride may work better in treating patients with Hodgkin lymphoma.

PRIMARY OBJECTIVE:

I. Evaluate the safety and tolerability of the combination of brentuximab vedotin (BV) plus MDR1 inhibitors cyclosporine (CsA)/verapamil hydrochloride (verapamil \[VRP\]).

SECONDARY OBJECTIVES:

I. Obtain estimates of overall response rate (ORR), complete response (CR) rate, and response duration in patients treated with the combination of BV plus CsA/VRP.

II. Estimate overall and progression-free survival in patients treated with the combination of BV plus CsA/VRP.

III. Characterize pharmacokinetics of plasma monomethyl auristatin E (MMAE) in cycle 1 (for expansion cohort only).

OUTLINE: This is a dose-escalation study of brentuximab vedotin and cyclosporine.

Patients receive cyclosporine orally (PO) twice daily (BID) on days 1-5, verapamil hydrochloride PO four times daily (QID) on days 1-5, and brentuximab vedotin intravenously (IV) over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients who have not progressed are followed up every 6 months until disease progression, start of a new lymphoma therapy, 2 years post treatment, or study completion, whichever is earlier. Patients who progress are followed up periodically.

Brentuximab Vedotin, Cyclosporine, and Verapamil Hydrochloride in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma

A Phase I Trial of Brentuximab Vedotin Plus MDR1 Inhibitors in Relapsed/Refractory Hodgkin Lymphoma

Expression by immunohistochemical staining.

Assessed by plasma concentration of MMAE in peripheral blood.

Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03.

Will be assessed by Cheson 2014 criteria. Will be estimated with the 95% exact binomial confidence interval.

Will be estimated with the 95% exact binomial confidence interval and using the product-limit method of Kaplan and Meier along with Greenwood estimator of standard error.

Will be estimated using the product-limit method of Kaplan and Meier along with Greenwood estimator of standard error.

Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. Observes toxicities will be summarized by type, severity, date of onset, duration, reversibility, and attribution.

National Cancer Institute (NCI)

City of Hope Medical Center

Spots Global Cancer Trial Database for verapamil hydrochloride